Allergy And Immunology On The Cusp Of Major Breakthroughs

Allergy and immunology is on the threshold of major therapeutic discoveries according to investigators presenting the latest research at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Philadelphia.

"Allergy and immunology is on the cusp of major breakthroughs based on a 40-year history of increasing our fundamental understanding of how the immune system and the allergic reaction part of the immune system works," said ACAAI President-Elect Daniel Ein, M.D., program chair for the meeting. He is clinical professor of medicine at George Washington University School of Medicine and chief of the division of allergy at GWU Medical Center, Washington, D.C.

"With that understanding comes the opportunity to target therapies in more specific ways," he said. "We've been attacking clinical problems with a broad approach, but we need to be more specific in the future with our therapies. It's the fulfillment of and logical extension of the last 40 years of basic research. We chose the meeting theme, 'We've Only Just Begun,' because I think we're in the early stages of a revolution in the treatment of allergic disease."

Allergen immunotherapy, a widely used approach, aims to modulate an allergic patient's immune response through administration of increasing doses of an extract which will eventually reduce or eliminate the patient's symptoms.

Although conventional subcutaneous immunotherapy has been shown to be effective for the treatment of allergic rhinitis, asthma and venom sensitivity, considerable research is being devoted to the development of therapeutic vaccines for the treatment of allergic diseases to improve efficacy, lessen the time to achieve effectiveness, reduce the inconvenience and enhance safety. Alternative methods of administration such as oral and sublingual are also being investigated.

Allergic Asthma

"There is a great need for novel therapies for asthma, especially in the 10 percent of severe asthmatics who account for approximately 50 percent of the health care costs of asthma," said David H. Broide, M.B., C.H.B., a professor of medicine at the University of California, San Diego.

"Although novel therapies frequently show promise in pre-clinical studies, only 8 percent of these therapies which are tested in human subjects prove to be safe and effective in humans with disease," Dr. Broide said.

The ability to find novel therapies that are safe and effective is complicated by the fact that asthma is not a single gene/protein/mediator disorder, and there are over 100 genes linked to asthma. Some novel therapies already in use include leukotriene inhibitors and anti-IgE therapy. Researchers are also studying the efficacy of a wide range of promising therapeutics such as antibiotics, probiotics and TLR (Toll Like Receptors) ligands, cytokines (Anti-TNF, Anti-IL-5), and transcription factors.

Anti-IgE (Omalizumab) is a humanized monoclonal antibody and the only therapy which targets IgE, the root cause of allergic asthma. It is the first biotechnology derived treatment for allergic asthma and was approved by the FDA in June 2003 for the treatment of patients diagnosed with moderate-to-severe forms of the disease.

Food Allergy

Researchers are also looking at novel approaches for treating food allergy, which is a major health problem in industrialized nations. It affects between 6 percent - 8 percent of young children and 4 percent of adults. Current management of food allergy includes the avoidance of specific foods and the medical management of acute reactions.

Only a few foods, such as milk, eggs, peanuts, nuts, and fish and shellfish account for over 90 percent of all food allergic reactions. Attempts at primary prevention have largely not met with much success.

"There are several promising studies being conducted now that likely will result in new treatments for food allergy," said Wesley Burks, M.D., professor and chief, Pediatric Allergy and Immunology at Duke University Medical Center, Durham, N.C.

One of the new therapies are on the horizon is Anti-IgE, which may be able to prevent severe food allergic reactions and can also be used in combination with other new therapies for treatment. Another is the use of modified allergenic proteins that may be able to "reverse" food allergy.

"Routes, other than subcutaneous, for the delivery of allergy immunotherapy for food allergy are being studied extensively now," said Dr. Burks.

Other Novel Therapies for Allergic Diseases

A number of studies are now evaluating the safety and efficacy of non-traditional forms of immunomodulation, including sublingual immunotherapy (SLIT) and oral immunotherapy (OIT). But while allergen-specific SLIT and OIT seem to hold some promise for patients with milder types of allergic disease, they have not been approved by the FDA for use in the United States. There is still a need for blinded, placebo controlled studies of correct dosing, multi-allergen therapy, and in patients with more severe allergic diseases.

Yet another novel approach currently under study is the use of an allergen vaccine with immunostimulatory DNA according to Peter S. Creticos, M.D., Johns Hopkins Asthma & Allergy Center, Baltimore, Md. The vaccine, which could be administered in a few doses, would have important therapeutic implications for millions of patients with poorly controlled allergic rhinitis and asthma, who would be ideal candidates for such a form of immunomodulation.

A novel immunostimulatory DNA vaccine called AIC, which is aimed at patients with allergies to ragweed, has already undergone preliminary testing in France, Canada, and the United States. Data from studies in Europe have confirmed the safety of AIC, and a recent clinical trial through the Immune Tolerance Network of the NIH has demonstrated promising results for efficacy. Patients with fall seasonal allergic rhinitis showed improvements in a number of different measures, including seasonal symptom diary scores, quality of life scores, and medication usage.

The results from these clinical studies of patients with ragweed-induced allergic rhinitis demonstrate that AIC is less allergenic than conventional immunotherapeutic products and may offer the potential for an improved safety profile for immunotherapy, Dr. Creticos said.

Patient information on allergic diseases including asthma is available by calling the ACAAI toll free number at (800) 842-7777 or visiting its Web site at http://www.acaai.org.

About ACAAI

The American College of Allergy, Asthma and Immunology (ACAAI) is a professional medical organization headquartered in Arlington Heights, Ill., that promotes excellence in the practice of the subspecialty of allergy and immunology. The College, comprising more than 5,000 allergists-immunologists and related health care professionals, fosters a culture of collaboration and congeniality in which its members work together and with others toward the common goals of patient care, education, advocacy and research.

American College of Allergy, Asthma and Immunology (ACAAI)
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http://www.acaai.org